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B-Cell Non-Hodgkin LymphomaPhase 1NCT03410901

TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas

A Phase 1 study testing Anti-OX40 Antibody BMS 986178, Laboratory Biomarker Analysis and Radiation Therapy in people with B-Cell Non-Hodgkin Lymphoma and Grade 1 Follicular Lymphoma, run by Ronald Levy at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-OX40 Antibody BMS 986178, Laboratory Biomarker Analysis and Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
9 Apr 2018to 10 Oct 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Biopsy confirmed low-grade B-cell lymphoma, excluding gastric MALT lymphoma, high-risk mantle cell lymphoma, and currently transformed lymphoma
  • Patients must have at least one site of disease (cervical, axillary, inguinal, or subcutaneous) that is accessible for intratumoral injection of SD-101 (diameter ≥10mm) percutaneously and presents a low risk for complications from direct injections.
  • Patients must have at least one site of measurable disease, other than the injection site, which is not included in the radiation field
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count (ANC) >= 1000/mm^3 independent of growth factor support
  • Platelets: >= 100,000/mm^3 or >= 50,000/mm^3 if known or suspected bone marrow involvement, independent of transfusion support in either situation
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  • Hemoglobin: >= 8 g/dL (may be transfused)
  • Creatinine: Creatinine clearance > 25 ml/min
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 3 x upper limit of normal (ULN)
  • Bilirubin: =< 1.5 x ULN (except for subjects with Gilbert's Syndrome or of non-hepatic cause)
  • Must be at least 4 weeks since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, any monoclonal antibodies or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during and after the study; for sexually active women of childbearing potential, these restrictions apply for 5 months after the last dose of study drug; for sexually active men, these restrictions apply for 7 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening, within 24 hours of the first dose of anti-OX40 antibody, and every four weeks while on study treatment; women who are pregnant or breastfeeding are ineligible for this study
  • Life expectancy greater than 3 months
  • Ability to comply with the treatment schedule
  • Ability to understand and willingness to sign a written informed consent document

Who cannot join

  • Currently transformed lymphoma, high-risk mantle cell lymphoma, or gastric MALT lymphoma.
  • Need for immediate treatment or cytoreduction.
  • No easily accessible site for direct percutaneous injection with low-risk for potential complications.
  • Autoimmune disease requiring treatment within the last 5 years including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, uveitis, or other if clinically significant
  • Major surgery within 4 weeks of enrollment, or a wound that has not fully healed
  • Vaccinated with live, attenuated vaccines within 4 weeks of enrollment
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  • Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection
  • Known central nervous system (CNS) lymphoma
  • Patients with a history of prior malignancy with the exception of non-melanoma skin cancer, stage 1 prostate cancer that does not require treatment, or other malignancy that has undergone potentially curative therapy with no evidence of disease for the last 2 years and that is deemed by the investigators to be at low risk for recurrence. In situ cancer of any type and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is not an exclusion, though if surgery or other definitive intervention is planned, it should be completed prior to enrollment.
  • History of significant allergic reactions attributed to compounds of similar composition to SD-101 or BMS-986178
  • Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study treatment; Note: patients may take up to 5 mg of prednisone or equivalent daily; topical and inhaled corticosteroids in standard doses are allowed
  • Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
  • Pregnant or breast feeding
  • Any other medical history, including laboratory results, deemed by the investigator likely to interfere with their participation in the study, or to interfere with the interpretation of the results

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University, School of Medicine

    Palo Alto, California, 94304

Other trials in United States

About this study

Official title: Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With BMS-986178 and Local Radiation in Low-Grade B-Cell Lymphomas

This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. Anti-OX40 antibody is a monoclonal antibody that enhances the activation of T cells, immune cells that are important for fighting tumors Radiation therapy uses high energy x-rays to kill cancer cells and may make them more easily detected by the immune system. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS 986178 and radiation therapy may work better in treating patients with low-grade B-cell non-hodgkin lymphomas.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and tolerability of TLR9 agonist SD-101 (SD-101) in combination with anti-OX40 antibody BMS 986178 (BMS-986178) and local low-dose radiation in patients with low-grade B-cell lymphoma. Adverse events and grades to be assessed by Common Terminology Criteria for Adverse Events (CTCAE) II. To determine the recommended phase 2 dose (RP2D) of BMS-986178 in combination with intratumoral SD-101 and radiation in patients with low-grade B-cell lymphoma.

SECONDARY OBJECTIVES:

  1. To evaluate preliminary efficacy by assessing overall response rate and progression-free survival after treatment with intratumoral SD-101 in combination with BMS-986178 and radiation in patients with low-grade B-cell lymphoma.

OUTLINE: This is a phase I study of the combination of TLR9 agonist SD-101, anti-OX40 antibody BMS 986178, and local low-dose radiation therapy.

Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 intravenously (IV) on days 3, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 72 weeks.

Being tested
Anti-OX40 Antibody BMS 986178, Laboratory Biomarker Analysis, Radiation Therapy, TLR9 Agonist SD-101
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-OX40 Antibody BMS 986178Biological

    Also called BMS 986178, BMS-986178

    Given IV, intratumoral

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation

    Undergo radiation therapy

  • TLR9 Agonist SD-101Drug

    Also called ISS-ODN SD-101, SD-101

    Given intratumorally

Study groups in NCT03410901
Study groupRoleWhat they receive
Treatment (radiation therapy, SD-101, BMS-986178)ExperimentalPatients receive radiation therapy on days 1-2, TLR9 agonist SD-101 and anti-OX40 antibody BMS-986178 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 IV on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Anti-OX40 Antibody BMS 986178; Other: Laboratory Biomarker Analysis; Radiation: Radiation Therapy; Drug: TLR9 Agonist SD-101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants experiencing Dose-limiting Toxicities (DLT) within 8 weeks of treatment initiation

    Dose-limiting toxicities (DLTs) as assessed as the following hematologic toxicities (grades per CTCAE) in all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178 (not including events due to disease progression or definitively unrelated to study drugs):

    • Febrile neutropenia
    • Thrombocytopenia Grade 4 or Grade 3 with bleeding or platelet transfusion
    • Anemia Grade 4
    • Non-hematological toxicity ≥ grade 3, except:
    • Alopecia controlled by medical management
    • Nausea controlled by medical management
    • Grade 3 or 4 electrolyte abnormalities not associated with adverse events, persist < 72 hours, and either spontaneously resolve or respond to intervention.
    • Grade 3 or 4 elevation of amylase or lipase not associated with pancreatitis
    • Grade 3 endocrinopathy
    • Grade 3 infusion reaction returning to ≤ Grade 1 in < 6 hours
    • Grade 3 skin rash not requiring systemic steroid or other immunosuppressive therapy

    Measured: Up to 8 weeks

Secondary outcomes (2)

  1. Overall Response Rate (ORR)

    Overall Response Rate (ORR), assessed as the sum of the complete response (CR) and partial response (PR) rates, as determined by computed tomography (CT) or positron emission tomography (PET)/CT and evaluated per the Lugano classification for low-grade B-cell lymphomas, in all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178.

    Lugano classification:

    • CR: No detectable disease by CT or PET/CT scan
    • PR: ≥ 50% decrease in size of target lesions
    • No response (NR) / Stable disease (SD): < 50% decrease in size of target lesions
    • Progressive disease (PD): Target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 cm or +50%.

    Reported for 24, 48, 72 and 96 weeks.

    Measured: Up to 96 weeks

  2. Progression-Free Survival (PFS)

    Progression-free survival (PFS) as determined for all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178, from start of treatment to disease progression per the Lugano classification or death from any cause, through 96 weeks. Progression assessed per the Lugano classification. Patients who were last known to be alive and progression-free will be censored at the latest disease assessment.

    Lugano classification:

    • CR: No detectable disease by CT or PET/CT scan
    • PR: ≥ 50% decrease in size of target lesions
    • No response (NR) / Stable disease (SD): < 50% decrease in size of target lesions
    • Progressive disease (PD): Target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 cm or +50%.

    Reported for 24, 48, 72 and 96 weeks.

    Measured: up to 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2018
  2. Study start9 Apr 2018
  3. Primary completion9 Oct 2024
  4. Study completion10 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03410901
Sponsor's protocol ID
IRB-44250
Other IDs
NCI-2017-02452, LYMNHL0144, R35CA197353
Status last verified
Dec 2024
First submitted
19 Jan 2018
Last updated
11 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382.

    PubMed 35135810

  • Mooney KL, Czerwinski DK, Shree T, Frank MJ, Haebe S, Martin BA, Testa S, Levy R, Long SR. Serial FNA allows direct sampling of malignant and infiltrating immune cells in patients with B-cell lymphoma receiving immunotherapy. Cancer Cytopathol. 2022 Mar;130(3):231-237. doi: 10.1002/cncy.22531. Epub 2021 Nov 15.

    PubMed 34780125

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-OX40 Antibody BMS 986178, Laboratory Biomarker Analysis and Radiation Therapy in people with B-Cell Non-Hodgkin Lymphoma and Grade 1 Follicular Lymphoma, run by Ronald Levy at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants experiencing Dose-limiting Toxicities (DLT) within 8 weeks of treatment initiation (time frame: Up to 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03410901, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.

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